PZI (Protamine Zinc Insulin) is a type of insulin combined with zinc and protamine
(a protein extracted from salmon) to slow the release of the
insulin into bodily tissue. It works well in controlling diabetes in many cats. PZI insulin production has undergone many changes in the last 5 years and is now generally a veterinary only insulin so you won't be able to buy it at a human pharmacy. If you chose to use PZI, it may only be available in U-40 strength (as opposed to the more common U-100 strength) and will require special syringes or use of a conversion chart if you only have U-100 syringes.

ProZinc®is the first and only FDA-approved insulin for cats made from recombinant DNA (DNA molecules created from the DNA of two unrelated organisms) that is identical to human insulin.
The ingredients in ProZinc ®(protamine zinc insulin) are classified as long-acting with duration of effect for 10-14 hours.

A number of veterinary pharmacies compound PZI, usually from 100% bovine insulin. Bovine insulin is a much better match for feline insulin than is human insulin and therefore works better in cats.

Why
use PZI?

Human insulin, in general, does not successfully replace the cat's
own insulin, and diabetes is not well-controlled in most cats when human (e.g. Humulin) insulin is used for treatment.>
Bovine (beef) insulin is most similar in molecular
structure to feline insulin, and it is thought for this reason, to be
most effective for these cats.

Although PZI is not generally considered the first choice for treatment of feline diabetes, many cats do well on PZI insulins. A scientific study has shown that 75% of previously treated hard-to-regulate cats were better controlled on PZI.[1] The study's author stated that most cats require PZI injections twice daily. Also, absorption, peak and duration of PZI is variable.

What about shelf
life?

Factors affecting shelf life of a vial that has been opened are:

exposure to light

accumulating contaminants from re-used syringes (or
even new syringes)

mixing with incompatible

lack of refrigeration
(loss of sterility)

chemical instability

Home testing
will enable you to determine for yourself whether the insulin is maintaining
its effectiveness. You should not use insulin that
suddenly looks different. PZI is clear (not cloudy) with white sediment
(no clumps), that when mixed gently, looks like watery milk. Compounded
insulins, as well as user-diluted or mixed insulins have an opened-life
of 30 to 90 days with reasonable care.

Which PZI should
I get?

It is impossible to predict which insulin will work best for your particular
cat. Two diabetic cats in the same household (i.e. same diet and schedule)
can respond differently to the same insulin.

If your cat doesn't respond even to large doses of human insulin, meaning
that blood sugar consistently stays very high despite doses larger than
1 unit per pound, and assuming there is not another serious problem causing
the high blood sugars, it makes good sense to try the compounded bovine PZI or the recombinant DNA ProZinc ®.

Most people with a newly diagnosed diabetic cat start treatment with
human insulins, injected twice a day, since they are widely available,
relatively inexpensive, and will work well for many cats. If you're inexperienced
(and/or have an inexperienced vet), and the insulin you're using "doesn't
work", realize that the insulin is only about half the treatment.
There's a great deal that you can learn to do to help the insulin (whatever
it is) work longer and better. Even if you've been around the block a
few times, if youre having difficulties, these points are worth
reviewing.

Many people turn to PZI because their cat
exhibits wide swings in blood sugar levels, from 400+ (or more) to sub-100's,
but with extremely variable (unpredictable) readings at all points on
the curve. Very often, this is due to giving too much insulin without
sufficient testing to see the whole cycle. If this is the case,
cutting the dose in half (or more) for several days and more frequent
testing will result in a flatter curve AND lower average numbers. Excessive
doses of insulin can mean steep roller coaster curves, with peak readings
(the insulin's strength is at its peak, and blood sugar is lowest) that
vary from being dangerously low, to being higher than desirable.
Large doses affect the insulin's duration as well, and may cause excessive
overlapping of the next dose (a sign of this is a dinner bg reading much
lower than the breakfast reading). If doses are overlapping, changing
doses "on the fly" is inadvisable because the effect of the
overlap on the next dose will always vary. It is most important
where overlap is suspected to find a minimal dose that can be given consistently.

Insulin acts to push blood sugar levels down,
diet is a major factor in what pushes blood sugars up. We try to balance
the effect of the insulin with the appropriate diet and feeding schedule
to obtain a flat curve in the target range (300 to 100mg/dl). With PZI,
as with any long-acting insulin, the role of diet cannot be overstated.
It is almost impossible to manage a large post-meal surge in blood sugar
with a long acting insulin such as PZI (or Ultralente), due to its slow
onset, and weak action. Trying to do so usually means excessively large
doses, steep curves and widely variable readings at shot time. You
can help a weak-acting insulin to control blood sugar by making dietary
changes, and you'll get flatter curves and lower numbers overall. To avoid
post-meal surges, make sure the diet (even if recommended by your old-school
vet) is low in CARBOHYDRATES. Dry cereals (especially diets created for
weight-loss) always have significantly more carbohydrates than wet food.
When switched to an improved, carbohydrate-restricted, high protein diet,
some cats produce enough insulin themselves and no longer need injected
insulin. Cats are carnivores, and require no more than 6% carbohydrate
(cereals contain as much as 30 or 40%). Purina
has done case studies (soon to be made public, 1-800-222-8387 for more
info) in which they observed that 93% of cats lower or eliminate insulin
requirements when fed their new canned food called Purina CNM DM-Formula
(prescription only). It is high in fiber and protein, low in carbohydrates.
If you're unable to halt the post-meal surges without large doses, even
with a corrected diet, consider trying a combination of a long-acting
insulin at 12-hour intervals to provide "fasting" coverage,
augmented at mealtimes with a fast-acting, short-duration insulin (use
2 syringes unless you know they're compatible. Usually only a fractional
unit of the fast-acting insulin is needed, so you can dilute it.) Caution:
substantially reducing carbohydrates in the diet is a POTENT factor in
reducing blood sugars and altering bg curves, and it should not be done
without also reducing insulin, and careful monitoring.

To get consistent curves, the diet must also
be consistent. Caloric intake and schedule should be the same, day to
day. If replacing dry food with canned food or "people food",
be careful to replace the calories as well; dry foods have 3 or 4 times
the calories, by weight. More calories require more insulin, fewer calories
require less. Other sources of inconsistency: free feeding in a multi-cat
household is not desirable. Canned foods may vary quite a bit in carbs
and calories, depending on the "flavor". Detailed nutritional
information can be obtained by calling the phone number listed on the
can or bag. Be sure to compare equal caloric amounts.

Increasing soluble fiber (metamucil, psillium
husks) is thought to slow and even out the process of digestion which
may flatten out the insulin's peak (the lowest point on the bg curve)
as well as moderate the post-meal rise in blood sugar. Be sure to monitor
carefully when adding fiber.

Just enough duration from the previous dose
to overlap the new dose while it's gaining strength is desirable. Too
much overlap will (sooner or later) drop blood sugar too much. Youre
aiming for 12-hour blood sugar values within around 10% of each other.
Remember that even before youve achieved regulation, you want a
gentle curve that gradually gets lower overall as dosage increases.
A steep drop from a very high reading, to a good peak cannot achieve
regulation in the end. 12-hour readings should be close enough
to each other that dosage can remain consistent. If the 12-hour
reading is so much lower that you cannot repeat the same dose consistently
(assuming that the peak will also be a lot lower), you will have a roller-coaster
situation where the affect of duration will always vary. The difference
between doses that are "too much" and "too little"
can be minute -- as little as a quarter-unit. If your cat is very sensitive
to small increments, consider the more dilute PZI from IDEXX (U40
strength) and use a U100 syringe if necessary (see "Strength"
discussion below). Unlike other insulin, diluting PZI yourself, is not
recommended.

Make sure that you're keeping a consistent
injection schedule, so that blood sugars don't get out of control due
to an injection given too late, and don't plummet because the injection
is given too early. What is "too late" and "too early"
will depend on the insulin's duration for your cat.

For various reasons, insulin may be absorbed
erratically, and this may affect large doses more than small ones. Avoid
using the scruff of the neck for injections, as there is insufficient
blood supply to that area. Rotate the injection site to avoid building
scar tissue and consequent absorption problems.

Certain conditions render bodily tissue insensitive
to insulin, this is called insulin resistance. Obesity is a major cause
of insulin resistance. One of the most effective (and most challenging)
ways for a fat cat to lower bg levels, and possibly eliminate the need
for injected insulin altogether, is by losing excess weight. Exercise,
smaller portions of a carb-restricted diet, reduced fat, or restriction
or elimination of treats are ways to accomplish weight loss. Note that
dry foods sold as low calorie, high fiber, for Seniors or
weight-loss may be higher in carbohydrates, lower in protein than normal
dry food (which is already higher in carbs than wet food), and should
not be given to diabetics. Something is wrong if your cat appears
to be "starving" -- he or she may have very high, or very low
blood sugar at that time -- it is not necessary or desirable to starve
your cat. High blood sugar alone is a major cause of insulin resistance
-- you will notice that the same dose will have more impact when given
at lower bg levels than at high levels.

Other causes for consistently high blood glucose
values are, pregnancy, stress, certain medications (corticosteroids),
infection (diabetics are especially susceptible to urinary infections)
and disease (renal, hyperthyroidism, liver disease and cancer to name
a few). These possibilities should be ruled out.

How Much Insulin is Too Much?

The Cornell University Feline Health Center has addressed the topic of
high insulin doses in cats. Excessively high insulin doses are those greater
than one to two units of insulin per pound per day. Felines who use more
insulin than this should be evaluated more intensively. Other diseases
may be underlying or complicating the diabetes mellitus and as a result,
necessitate high insulin dosages. Problems with insulin injection, poor
absorption or too rapid metabolism of insulin, or even insulin overdose
are potential causes of an apparently excessive insulin requirement.